chr12-2691052-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000719.7(CACNA1C):c.6270C>T(p.Pro2090Pro) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000657 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CACNA1C
NM_000719.7 synonymous
NM_000719.7 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.81
Genes affected
CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CACNA1C | NM_000719.7 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | ENST00000399655.6 | NP_000710.5 | |
| CACNA1C | NM_001167623.2 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | ENST00000399603.6 | NP_001161095.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CACNA1C | ENST00000399603.6 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | 5 | NM_001167623.2 | ENSP00000382512.1 | ||
| CACNA1C | ENST00000399655.6 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | 1 | NM_000719.7 | ENSP00000382563.1 | ||
| CACNA1C | ENST00000682544.1 | c.6609C>T | p.Pro2203Pro | synonymous_variant | 50/50 | ENSP00000507184.1 | ||||
| CACNA1C | ENST00000406454.8 | c.6483C>T | p.Pro2161Pro | synonymous_variant | 48/48 | 5 | ENSP00000385896.3 | |||
| CACNA1C | ENST00000399634.6 | c.6450C>T | p.Pro2150Pro | synonymous_variant | 47/47 | 5 | ENSP00000382542.2 | |||
| CACNA1C | ENST00000683824.1 | c.6435C>T | p.Pro2145Pro | synonymous_variant | 48/48 | ENSP00000507867.1 | ||||
| CACNA1C | ENST00000347598.9 | c.6414C>T | p.Pro2138Pro | synonymous_variant | 49/49 | 1 | ENSP00000266376.6 | |||
| CACNA1C | ENST00000344100.7 | c.6393C>T | p.Pro2131Pro | synonymous_variant | 47/47 | 1 | ENSP00000341092.3 | |||
| CACNA1C | ENST00000327702.12 | c.6375C>T | p.Pro2125Pro | synonymous_variant | 48/48 | 1 | ENSP00000329877.7 | |||
| CACNA1C | ENST00000399617.6 | c.6375C>T | p.Pro2125Pro | synonymous_variant | 48/48 | 5 | ENSP00000382526.1 | |||
| CACNA1C | ENST00000682462.1 | c.6360C>T | p.Pro2120Pro | synonymous_variant | 47/47 | ENSP00000507105.1 | ||||
| CACNA1C | ENST00000683781.1 | c.6360C>T | p.Pro2120Pro | synonymous_variant | 47/47 | ENSP00000507434.1 | ||||
| CACNA1C | ENST00000683840.1 | c.6360C>T | p.Pro2120Pro | synonymous_variant | 47/47 | ENSP00000507612.1 | ||||
| CACNA1C | ENST00000683956.1 | c.6360C>T | p.Pro2120Pro | synonymous_variant | 47/47 | ENSP00000506882.1 | ||||
| CACNA1C | ENST00000399638.5 | c.6354C>T | p.Pro2118Pro | synonymous_variant | 48/48 | 1 | ENSP00000382547.1 | |||
| CACNA1C | ENST00000335762.10 | c.6345C>T | p.Pro2115Pro | synonymous_variant | 48/48 | 5 | ENSP00000336982.5 | |||
| CACNA1C | ENST00000399606.5 | c.6330C>T | p.Pro2110Pro | synonymous_variant | 48/48 | 1 | ENSP00000382515.1 | |||
| CACNA1C | ENST00000399621.5 | c.6327C>T | p.Pro2109Pro | synonymous_variant | 47/47 | 1 | ENSP00000382530.1 | |||
| CACNA1C | ENST00000399637.5 | c.6327C>T | p.Pro2109Pro | synonymous_variant | 47/47 | 1 | ENSP00000382546.1 | |||
| CACNA1C | ENST00000402845.7 | c.6327C>T | p.Pro2109Pro | synonymous_variant | 47/47 | 1 | ENSP00000385724.3 | |||
| CACNA1C | ENST00000399629.5 | c.6321C>T | p.Pro2107Pro | synonymous_variant | 47/47 | 1 | ENSP00000382537.1 | |||
| CACNA1C | ENST00000682336.1 | c.6312C>T | p.Pro2104Pro | synonymous_variant | 47/47 | ENSP00000507898.1 | ||||
| CACNA1C | ENST00000399591.5 | c.6294C>T | p.Pro2098Pro | synonymous_variant | 46/46 | 1 | ENSP00000382500.1 | |||
| CACNA1C | ENST00000399595.5 | c.6294C>T | p.Pro2098Pro | synonymous_variant | 46/46 | 1 | ENSP00000382504.1 | |||
| CACNA1C | ENST00000399649.5 | c.6288C>T | p.Pro2096Pro | synonymous_variant | 46/46 | 1 | ENSP00000382557.1 | |||
| CACNA1C | ENST00000399597.5 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | 1 | ENSP00000382506.1 | |||
| CACNA1C | ENST00000399601.5 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | 1 | ENSP00000382510.1 | |||
| CACNA1C | ENST00000399641.6 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | 1 | ENSP00000382549.1 | |||
| CACNA1C | ENST00000399644.5 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | 1 | ENSP00000382552.1 | |||
| CACNA1C | ENST00000682835.1 | c.6270C>T | p.Pro2090Pro | synonymous_variant | 47/47 | ENSP00000507282.1 | ||||
| CACNA1C | ENST00000683482.1 | c.6261C>T | p.Pro2087Pro | synonymous_variant | 47/47 | ENSP00000507169.1 | ||||
| CACNA1C | ENST00000682686.1 | c.6237C>T | p.Pro2079Pro | synonymous_variant | 46/46 | ENSP00000507309.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000432 AC: 1AN: 231296Hom.: 0 AF XY: 0.00000791 AC XY: 1AN XY: 126350
GnomAD3 exomes
AF:
AC:
1
AN:
231296
Hom.:
AF XY:
AC XY:
1
AN XY:
126350
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1454398Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 722882
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1454398
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
722882
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74334
GnomAD4 genome
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74334
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 33
Find out detailed SpliceAI scores and Pangolin per-transcript scores at